title: Attenuated Salmonella typhimurium carrying shRNA-expressing vectors elicit RNA interference in murine bladder tumors.
abstract: OBJECTIVE
  To examine whether attenuated Salmonella typhimurium (S typhimurium) could be used as an anti-cancer agent or a tumor-targeting vehicle for delivering shRNA-expressing pDNA into cancer cells in a mouse tumor model.
  
  
  METHODS
  Mouse bladder transitional cancer cell line (BTT-T739) expressing GFP was used, in which the GFP expression level served as an indicator of RNA interference (RNAi). BTT-T739-GFP tumor-bearing mice (4-6 weeks) were treated with S typhimurium carrying plasmids encoding shRNA against gfp or scrambled shRNA. The mRNA and protein expression levels of GFP were assessed 5 d after the bacteria administration, and the antitumor effects of S typhimurium were evaluated.
  
  
  RESULTS
  In BTT-T739-GFP tumor-bearing mice, S typhimurium (1×10(9) cfu, po) preferentially accumulated within tumors for as long as 40 d, and formed a tumor-to-normal tissue ratio that exceeded 1000/1. S typhimurium carrying plasmids encoding shRNA against gfp inhibited the expression of GFP in tumor cells by 73.4%. Orally delivered S typhimurium significantly delayed tumor growth and prolonged the survival of tumor-bearing mice.
  
  
  CONCLUSIONS
  This study demonstrates that attenuated S typhimurium can be used for both delivering shRNA-expressing vectors into tumor cells and eliciting RNAi, thus exerting anti-tumor activity, which may represent a new strategy for the treatment of solid tumors.
authors.affiliation: Instititute of Genetics, School of Life Sciences, Fudan University, Shanghai, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Yang
authors.forename: Sheng-hua
authors.initials: SH
authors.lastname: Li
authors.forename: Yun-zhe
authors.initials: YZ
authors.lastname: Lü
authors.forename: Li-shan
authors.initials: LS
authors.lastname: Chen
authors.forename: Da-ming
authors.initials: DM
authors.lastname: Ren
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D005822:Genetic Vectors; D051379:Mice; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics* / Q000378:metabolism; D012486:Salmonella typhimurium / Q000235:genetics* / Q000378:metabolism / Q000472:pathogenicity; D001749:Urinary Bladder Neoplasms / Q000628:therapy*
chemical_list: D034741:RNA, Small Interfering